Skeletal dysplasia
Gene: ABL1
>3 families reported - Y245C in several. Skeletal defects are variable and include pectus excavatum, scoliosis, and finger contractures, and some patient exhibit joint laxity. Rating: green if SD; Review on behalf of Tracy LesterCreated: 6 Mar 2019, 11:44 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Congenital heart defects and skeletal malformations syndrome, 617602
Publications
Comment on list classification: Leaving this gene as amber just now. Question as to whether this is considered a skeletal dysplasia. The broader skeletal manifestations (scoliosis / pectus) are classically thought of as part of the Marfan / FTAAD spectrum rather than a skeletal dysplasia.Created: 11 Dec 2019, 5:02 p.m. | Last Modified: 11 Dec 2019, 5:02 p.m.
Panel Version: 1.282
This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: ABL1; Initial rating suggestion: green if SDCreated: 6 Mar 2019, 11:36 a.m.
Comment on mode of pathogenicity: Seleced 'LOF do not cause this phenotype' on advice from Helen Brittain, Clinical Fellow, in view of the postulated gain of function mechanism (two recurent missense variants in PMID:28288113).Created: 6 Dec 2018, 9:29 p.m.
Added to Skeletal dysplasia panel with Amber rating as suggested by Helen Brittain. Wang et al, 2017 (PMID:28288113) report ABL1 germline variants cosegregating with an autosomal dominant disorder characterized by congenital heart disease, skeletal abnormalities and failure to thrive. They report 2 variants in 4 families (6 individuals). Helen Brittain, clinical fellow, notes that: "the broader skeletal manifestations (scoliosis / pectus) are classically thought of as part of the Marfan / FTAAD spectrum rather than a skeletal dysplasia. Therefore do not think that skeletal dysplasia (or limb panel) would be the primary route for diagnosis here and would opt for amber on the basis that we need to see the phenotype across other cases first."
Sources: LiteratureCreated: 6 Dec 2018, 9:28 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Congenital heart defects and skeletal malformations syndrome, 617602
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Gene: abl1 has been classified as Amber List (Moderate Evidence).
Added phenotypes Congenital heart defects and skeletal malformations syndrome, 617602 for gene: ABL1
Source NHS GMS was added to ABL1.
Mode of pathogenicity for gene: ABL1 was changed from Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Gene: abl1 has been classified as Amber List (Moderate Evidence).
gene: ABL1 was added gene: ABL1 was added to Skeletal dysplasia. Sources: Literature missense tags were added to gene: ABL1. Mode of inheritance for gene: ABL1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: ABL1 were set to 28288113 Phenotypes for gene: ABL1 were set to Congenital heart defects and skeletal malformations syndrome, 617602 Mode of pathogenicity for gene: ABL1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments